Using pharmacology and optogenetics perturbations, we showed that cortical brain-derived neurotrophic factor (BDNF) regulates the intensity of SWA via the activation of Tyrosine kinase B (TrkB) receptor and cAMP-response element-binding protein (CREB). We identified that the circuitry mediating TrkB-induced sleep SWA involves excitatory pyramidal cells of the cortex's layer 5. We found that increased neuronal firing alone in the somatosensory cortex was not sufficient to increase SWA. Using mathematical modeling of a local network in the brain, we model how BDNF’s effects on synaptic strength can increase SWA in ways not achieved through increased firing alone. Together, our findings implicate BDNF-TrkB-CREB signaling pathway in local SWA control during sleep.